Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-three patients with low natural killer syndrome (LNKS), 7 males and 16 females, are reported here. These LNKS patients had an age range from 14 to 77 years, with a median of 36.5 years. LNKS is a newly proposed category of immune disorders, being characteristically diagnosed by lowered NK cell activity against K562 target cells as a definite laboratory abnormality, in association with general clinical symptoms of remittent fever and uncomfortable fatigue, persisting without explanation for more than 6 months. Other immune parameters, such as the DNA synthesis of peripheral blood mononuclear cells (PBMCs) in either the presence or absence of mitogens, the T4+/T8+ ratio and the number of Leu-11+ PBMCs, were usually within the normal range. Also, routine laboratory tests did not detect any abnormal findings. The LNKS patients responded well to the administration of an immunopotentiator called 'lentinan', a glucan extracted from the Japanese mushroom Lentinus edodes, despite no responses to conventional fever treatments such as the administration of antipyretics or antibiotics. All LNKS patients observed were universally free of antibodies in their sera to human T-lymphotropic retroviruses I and III, and lymphadenopathy was infrequent, indicating that the LNKS is a syndrome independent of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Antibodies to other known viruses tested such as Epstein-Barr or measles virus, or cytomegalovirus were also negative or not significantly elevated in the sera before the initiation of lentinan administration. If a virus is the cause of LNKS, it may be a new, unknown virus or an unknown substrain of known viruses. None of the LNKS patients has died of this syndrome.
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PMID:Low natural killer syndrome: clinical and immunologic features. 244 2

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologic response modifiers: the interferon alfa experience. 248 96

AIDS-related gastrointestinal disease is common, presenting a challenge to all nutritional support clinicians. Patients frequently suffer from weight loss, diarrhea, malabsorption, and cachexia. Many factors complicate the course of AIDS-related gastrointestinal disease, including decreased food intake (resulting from fatigue and malaise), increased metabolic demand and nutritional requirements, and identifiable gastrointestinal pathology. Gastrointestinal pathology is well-documented, and in approximately 50% of persons with AIDS-related gastrointestinal disease, a causative agent can be identified. In general, treatment of AIDS-related gastrointestinal disease is not always curative. Much of the chronic gastrointestinal dysfunction is caused by recurring opportunistic pathogens that are resistant to chemotherapy. Often, patient care and long-term management can focus only on fluid and electrolyte balance, nutritional support, and symptom control. Even clinically stable patients have been diagnosed as chronically malnourished and, for reasons that remain unclear, are prone to rapid nutritional deterioration during disease exacerbations. Published reports of nutritional assessment and intervention in persons with AIDS are now appearing in the literature. However, the eventual mortality associated with AIDS still results in a hesitancy on the part of many clinicians to prescribe aggressive nutritional support, especially parenteral nutrition. Who to treat and at what stage of illness becomes the question. As new agents, such as AZT, are prescribed on a more frequent basis for persons with AIDS, the use of nutritional support as adjunctive therapy early in the course of disease becomes an issue. Although improving nutrition has not been shown to reverse any of the cellular immunodeficiency caused by HIV infection, quality of life may be improved. In specific cases, nutritional support, whether through diet counseling, food programs, or intervention with enteral or parenteral nutrition, appears to improve strength and endurance, thus enhancing quality of life.
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PMID:Gastrointestinal manifestations of the acquired immunodeficiency syndrome. 249 50

To characterize the nature, time course and dose dependency of zidovudine-related side effects, we undertook a multicenter, prospective, dose-range finding study. Our study group consisted of 74 HIV-positive homosexual men belonging to groups II B, III and IV C2 from the Centers for Disease Control (CDC) classification of HIV disease. Following a 3-week observation period, volunteers were treated with zidovudine 600 mg/day for 18 weeks, 900 mg/day for 9 weeks and 1200 mg/day for 9 weeks, followed by a washout period of 6 weeks after which they were re-started on 1200 mg/day or the highest tolerated dose at 8-hourly intervals. Subjects were randomly assigned to 4-hourly or 8-hourly regimens within CDC groups while taking 600 and 1200 mg/day. Clinical and laboratory evaluations were performed at 3-week intervals. Symptomatic adverse effects were present in 96% of subjects, most commonly nausea (64%), fatigue (55%) and headache (49%). These were generally self-limited, reappearing briefly at each dose increment. A decrease in hemoglobin occurred shortly after initiation of therapy. This was not dose dependent and reversed rapidly upon discontinuation of treatment. A red blood cell count decrease, a mean cell volume increase and a granulocyte count decrease developed early in a dose-independent fashion, reverting at least partially during the washout phase. The decrease in reticulocyte count was dose related between 600 and 900 mg/day with no further change when the dose was escalated to 1200 mg/day. Bone marrow changes occurred rapidly as demonstrated by megaloblastosis in 95% of 65 specimens at week 18.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS 1989 Sep
PMID:Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial. 252 69

A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD.
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PMID:A phase I trial of recombinant human interferon-gamma in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS). 254 86

The characteristics and clinical uses of recombinant colony-stimulating factors (CSFs) are described, and the pharmacist's role as a consultant and educator on biotherapeutic substances is discussed. CSFs stimulate the formation and differentiation of the erythrocytes, neutrophils, eosinophils, basophils, monocytes, and platelets that compose the blood cell population. Recombinant CSFs represent a means by which the numbers of hematopoietic cells can be modulated, thus making these agents potentially useful in treating hematologic and immunologic deficiencies. CSFs also can increase the ability of neutrophils and monocyte-macrophages to protect the body against foreign invasion. Granulocyte macrophage colony-stimulating factor (GM-CSF) has increased host defenses in acquired immunodeficiency syndrome patients with Kaposi's sarcoma; increased neutrophil, platelet, and erythrocyte counts in preleukemic patients; and increased neutrophil counts in patients with aplastic anemia. GM-CSF and granulocyte colony-stimulating factor (G-CSF) have appeared to alleviate the drastic decrease in neutrophil counts associated with cytotoxic chemotherapy. G-CSF also has shown promise in stimulating neutrophil production in patients with transitional cell carcinoma, congenital agranulocytosis, and hairy-cell leukemia. Mild adverse effects such as fever, chills, rash, fatigue, myalgia, and bone pain are associated with GM-CSF therapy; G-CSF therapy is associated mostly with mild to moderate bone pain. Areas of education for pharmacists working with biotherapeutic substances include stability, storage temperature, drug interactions, novel drug-delivery systems such as monoclonal antibodies or liposomes, variations in biologic activity, and the evolving nature of the information about these investigational drugs. The pharmacist can anticipate an increasing role as a consultant on the use of CSFs and other biotherapeutic substances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony-stimulating factors and tomorrow's pharmacy: why we must be ready. 269 Jun 7

Seventy-four sequential lymph node biopsies from 30 acquired immunodeficiency syndrome (AIDS)/AIDS-related complex (ARC) patients showed temporal histologic progression from explosive follicular hyperplasia (EFH) to mixed follicular hyperplasia/involution (mixed) to follicular involution (FI) to lymphocyte depletion (LD). This histologic progression correlated with symptoms, development of opportunistic infections (OI), and mortality. At initial biopsy, only 50% of the AIDS/ARC patients with EFH/mixed compared to 100% with FI/LD were symptomatic with weight loss, night sweats, diarrhea, fever, or fatigue. 31% of ARC patients with EFH and 63% with FI developed an OI in a median of 69 months and 5 months, respectively; 86% with LD had a concurrent or previous OI. Ninety percent of ARC patients progressing to FI/LD died; 85% of those persisting with EFH/mixed remained alive 18 to 50 months after initial biopsy. AIDS patients with EFH lived twice as long as those with FI/LD. Progressive histology did not correlate with lymphoma. The number of ARC patients developing Kaposi's sarcoma was too small to draw definitive conclusions.
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PMID:Progressive lymph node histology and its prognostic value in patients with acquired immunodeficiency syndrome and AIDS-related complex. 272 79

A group of men with AIDS who chose to follow a macrobiotic regimen as an alternative form of therapy was studied for the possible influence of psychological factors on their clinical progression. In this group, men with Kaposi's sarcoma (KS) had an estimated survival time of 60% at 3 years. Moreover, there was a tendency for lymphocyte number to increase during the first 3 years following diagnosis with KS. A subset of eight of these men with KS and one man with Pneumocystis carinii pneumonia (PCP) agreed to fill out a battery of psychological questionnaires. The results suggest low levels of fatigue, negative affect, and confusion, but high levels of vigor in this subgroup. Additionally, there was significant positive associations of CD4 positive lymphocyte numbers with trait curiosity and hardiness scores and significant negative associations with anxiety and depression. Mitogen responsiveness followed a similar pattern, but only a positive association with curiosity reached significance. Caution has to be used in interpreting such data, especially in view of the size of the sample and the complexity of the cohort. Nonetheless, these findings clearly suggest the need for prospective studies on the influence of psychological factors on the progression of AIDS.
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PMID:Psychological and immunological associations in men with AIDS pursuing a macrobiotic regimen as an alternative therapy: a pilot study. 279 Feb 32

Early pathological abnormalities in human immunodeficiency virus (HIV-1)-related dementia have not been well documented. We report a homosexual man with fatigue and intermittent diarrhea in whom early HIV-1-related dementia was demonstrated during neurological screening in the Multicenter AIDS Cohort Study. Within 4 months he died of massive epistaxis, and the brain revealed astrocytosis of white matter and mild pallor of myelin staining in the absence of inflammation, multinucleated giant cells, and brain atrophy.
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PMID:Neuropathological changes in early HIV-1 dementia. 281 44

During a prospective study of the natural history of human immunodeficiency virus (HIV) infection in a cohort of gay/bisexual men, information on self-reported symptoms lasting for 3 or more days during the previous 6 months was collected without knowledge of the subject's HIV serological status. Twenty-two people were retrospectively found to have seroconverted to HIV during the interval. Each seroconverter was matched to two seronegative and two seropositive controls. Matched case-control analyses using the seronegative controls determined that the following symptoms lasting for 3 or more days were associated with new HIV infection: fever greater than 37.7 degrees C, swollen lymph nodes, night sweats and headaches. Matched case-control analyses using the seropositive controls determined that the following symptoms lasting for 3 or more days were associated with new HIV infection: fatigue, fever greater than 37.7 degrees C, swollen lymph nodes, night sweats and headaches. It was notable that the majority of seroconversions were not associated with any symptoms lasting for 3 or more days. Due to their non-specificity, symptoms associated with seroconversion are not likely to have a high positive predictive value. In high risk populations, however, appearance of these symptoms may facilitate identification of early infection that may be important for studies of natural history or for optimal timing for initiating antiviral therapy.
AIDS 1987 May
PMID:Clinical manifestations of acute infection with human immunodeficiency virus in a cohort of gay men. 312 87


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